Information on EC 2.7.11.4 - [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase

ATP + mitogen-activated protein kinase kinase

ADP + phosphorylated mitogen-activated protein kinase kinase

ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)]

ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate

9 entries

ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]

ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate

34 entries

ATP + [branched-chain a-keto acid dehydrogenase (acetyl-transferring)]

ADP + [branched-chain a-keto acid dehydrogenase (acetyl-transferring)] phosphate

-

739507

-

?

ATP + [branched-chain keto-acid dehydrogenase (acetyl-transferring)]

ADP + [branched-chain keto-acid dehydrogenase (acetyl-transferring)] phosphate

Q00972

the enzyme phosphorylates Ser293 of the E1alpha subunit of branched-chain keto-acid dehydrogenase

739455

-

?

additional information

?

-

5 entries

ATP + branched-chain alpha-keto acid decarboxylase/dehydrogenase

ADP + phosphorylated branched-chain alpha-keto acid decarboxylase/dehydrogenase

ATP + mitogen-activated protein kinase kinase

ADP + phosphorylated mitogen-activated protein kinase kinase

O13874

the enzyme promotes cell transformation or colorectal cancer by enhancing the MAPK signaling pathway through direct MEK phosphorylation

760972

-

?

ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)]

ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate

7 entries

ATP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]

ADP + [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)] phosphate

8 entries

ATP + [branched-chain a-keto acid dehydrogenase (acetyl-transferring)]

ADP + [branched-chain a-keto acid dehydrogenase (acetyl-transferring)] phosphate

-

739507

-

?

ATP + [branched-chain keto-acid dehydrogenase (acetyl-transferring)]

ADP + [branched-chain keto-acid dehydrogenase (acetyl-transferring)] phosphate

Q00972

the enzyme phosphorylates Ser293 of the E1alpha subunit of branched-chain keto-acid dehydrogenase

739455

-

?

additional information

?

-

ATP

Calmodulin

-

activation

EGTA

K+

Mg2+

Rb+

-

activation

640581

additional information

(2R)-2-chloro-3-phenylpropanoic acid

-

(2S)-2-chloro-3-phenylpropanoic acid

-

(R)-alpha-chloroisocaproate

-

(S)-alpha-chloroisocaproate

-

2-(N-Morpholino)propane sulfonate buffer

2-Chloroisohexanoate

9 entries

2-oxo-3-methylpentanoate

4 entries

2-oxobutanoate

-

349056

2-oxohexanedioate

2-Oxohexanoate

-

2-oxoisocaproate

2-oxoisopentanoate

2-oxopentanoate

3,6-dichlorobenzo[b]thiophene-2-carboxylic acid

3-chloro-6-fluorobenzo[b]thiophene-2-carboxylic acid

3-methyl-2-oxobutanoate

-

4-(2-Thienyl)-2-oxo-3-butenoate

-

2 mM

4-(3-Thienyl)-2-oxo-3-butenoate

-

2 mM

4-hydroxyphenylacetate

-

640578

4-hydroxyphenyllactate

-

weak

640578

4-hydroxyphenylpyruvate

4-methyl-2-oxopentanoate

-

acetate

-

weak, in vivo and in vitro

640578

acetoacetyl-CoA

5 entries

acyl-CoA

-

ADP

9 entries

alpha-Chloroisocaproate

alpha-Ketoisocaproate

-

inhibits the enzyme by releasing it from the BCKD complex via dissociation

662695

alpha-ketoisovalerate

-

inhibits the enzyme by releasing it from the BCKD complex via dissociation

662695

ATP

branched-chain 2-oxo acids

Ca2+

CDP

-

50% inhibition at 0.4 mM, inhibition can be reversed by 2 mM Mg2+

Clofibric acid

CoA

-

CTP

-

50% inhibition at 0.25 mM, inhibition can be reversed by 2 mM Mg2+

dexamethasone

Sus scrofa

-

decreases enzyme expression level in renal tubule cells

Dichloroacetate

diphosphate

-

Furfurylidenepyruvate

-

1.85 mM

GDP

-

50% inhibition at 0.2 mM, inhibition can be reversed by 2 mM Mg2+

GTP

-

50% inhibition at 0.06 mM, inhibition can be reversed by 2 mM Mg2+

heparin

Hydrocinnamic acid

-

isobutyryl-CoA

-

349056, 640579

isovaleryl-CoA

-

349056, 640579

malonyl-CoA

-

349056, 640579

methylhydrocinnamic acid

-

methylmalonyl-CoA

Mg2+

-

at concentrations above 1.5 mM, activation below

349056

MgATP2-

-

N,N'-(1,2,5-oxadiazole-3,4-diyl)bis(3,6-dichlorobenzo[b]thiophene-2-carboxamide

N-(4-acetamido-1,2,5-oxadiazol-3-yl)-3,6-dichlorobenzo[b]thiophene-2-carboxamide

n-Octanoate

NADP+

octanoic acid

-

phenylacetate

phenylbutyrate

-

Phenyllactate

phenylpyruvate

-

in vivo and in vitro

phenylpyruvic acid

-

pyruvate

thiamine

-

thiamine diphosphate

trioctanoin

-

UDP

-

50% inhibition at 0.25 mM, inhibition can be reversed by 2 mM Mg2+

UTP

-

50% inhibition at 0.1 mM, inhibition can be reversed by 2 mM Mg2+

additional information

14 entries

-

histone H3

-

1.5 to 3fold

-

poly-L-arginine

-

1.5 to 3fold

poly-L-lysine

-

1.5 to 3fold

protamine

-

1.5 to 3fold

additional information

-

0.004 - 0.025

ATP

7 entries

0.0542 - 0.475

phosphate

0.5

2-Chloroisohexanoate

-

37°C

349052

0.00092

2-oxoisocaproate

-

pH 7.5, 30°C

0.00048 - 0.0089

4-methyl-2-oxopentanoate

0.00027 - 0.27

ADP

4 entries

0.004

diphosphate

-

pH 7.5, 30°C

4.5

Furfurylidenepyruvate

-

0.0059

thiamine

-

pH 7.5, 30°C

0.0032 - 0.0164

thiamine diphosphate

0.0214

(2R)-2-chloro-3-phenylpropanoic acid

Mus musculus

at pH 7.5 and 25°C

0.0063

(2S)-2-chloro-3-phenylpropanoic acid

Mus musculus

at pH 7.5 and 25°C

0.012

(R)-alpha-chloroisocaproate

Mus musculus

at pH 7.5 and 25°C

0.0534

(S)-alpha-chloroisocaproate

Mus musculus

at pH 7.5 and 25°C

0.0749

2-oxoisocaproate

Mus musculus

at pH 7.5 and 25°C

0.00319

3,6-dichlorobenzo[b]thiophene-2-carboxylic acid

0.006 - 0.031

alpha-Chloroisocaproate

0.812

Clofibric acid

Mus musculus

at pH 7.5 and 25°C

0.0431

Hydrocinnamic acid

Mus musculus

at pH 7.5 and 25°C

0.0338

methylhydrocinnamic acid

Mus musculus

at pH 7.5 and 25°C

1.27

phenylacetate

Mus musculus

at pH 7.5 and 25°C

0.0531

phenylbutyrate

Mus musculus

at pH 7.5 and 25°C

0.346

phenylpyruvic acid

Mus musculus

at pH 7.5 and 25°C

0.0025 - 0.008

thiamine diphosphate

0.0247

-

without added salt

640581

0.0268

-

liver enzyme

640585, 640598

0.0357

-

heart enzyme

640585

0.0357 - 0.09

-

heart enzyme, depending on purification method

0.05

-

recombinant enzyme

additional information

4 entries

7.1

-

349073

7.4

-

assay at

640595, 656230

7.5

-

349056

additional information

6.5 - 8.3

-

about half-maximal activity at pH 6.5 and 8.3

349073

22

-

assay at room temperature

30

37

8.5

-

native PAGE

640589

-

94884, 349051, 349056, 640575, 640576, 640577, 640583, 640588

-

Mus musculus C57/BL6J

mouse, C57BL/6J

640590, 640591

-

-

94884, 349052, 349056, 349073, 640578, 640579, 640580, 640583

-

Rattus norvegicus Sprague-Dawley

10 entries

Sprague-Dawley

-

-

-

-

-

liver cell line

-

undifferentiated myoblast cell line

662283

colonic cancer cell line

O13874

the enzyme (BCKDK) is widely expressed in colorectal cancer patients, and patients that express higher levels of BCKDK have shorter survival times than those with lower levels

-

-

-

LLC-PK1 renal tubule cell line expressing the Rattus norvegicus glucocorticoid receptor GR

-

Q14874

-

-

-

-

-

fibroblast cell line

-

-

additional information

malfunction

metabolism

-

the enzyme is involved in the regulation of the branched-chain alpha-keto acid dehydrogenase complex by inactivating it through phopshorylation, complex regulation and effects of the drug benzofibrate, overview

723788

physiological function

5 entries

additional information

-

activity of BDK practically corresponds with plasma insulin concentrations

721483

12 entries

2000000

-

above 2000000, gel filtration

349056, 349073

43000

-

1 * 43000, uncomplexed kinase, SDS-PAGE

640588

43280

-

calculated from amino acid sequence

640587

44000

-

x * 44000, SDS-PAGE

640585

44000 - 45000

-

SDS-PAGE

460000

-

gel filtration

?

dimer

dimerizes through direct interaction of two opposing nucleotide-binding domains, crystallographic data

640594

monomer

-

1 * 43000, uncomplexed kinase, SDS-PAGE

640588

in complex with 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid

Q14874

738618

in complex with (S)-alpha-chloro-phenylpropionic acid, hanging drop vapor diffusion method, using 12% (w/v) PEG-8000, 0.1 M Tris·HCl, pH 8.5, 1.3-1.5 M NaCl

in complex with 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid

738618

vapor diffusion method

G671C

-

naturally occuring mutation, on chromosome 16, leads to the substitution of a highly conserved arginine with a proline at position 224 in BCKDK

723772

L389P

Q14874

the mutation is associated with developmental delay, microcephaly, and neurobehavioral abnormalities

738353

R174G

Q14874

the mutation is associated with developmental delay, microcephaly, and neurobehavioral abnormalities

738353

R224P

-

naturally occuring mutation, leading to disruption of the beta sheet in a flexible linker domain, structure modeling

723772

additional information

7

-

loss of activity during purification at pH-values below 7

640575

precipitation of branched-chain oxo acid dehydrogenase enzyme complex at acid pH-values, especially below 6.5, results in specific loss of kinase activity

labile enzyme, best stored at -70°C in the presence of DTT

-

-

5000fold

-

alpha-ketoacid dehydrogenase complex

copurifies with EC 1.2.4.4

-

640576

from liver and heart, homogeneity

-

640583

from purified branched-chain alpha-keto acid dehydrogenase complex

-

640585

liver enzyme, heart enzyme and recombinant enzyme expressed in Escherichia coli

-

partially from mitochondria

Sus scrofa

-

660683

-

BCKD kinase transcription regulation, overview

Sus scrofa

-

660683

BDK quantitative real-time PCR expression analysis

-

721483

BDK semi-quantitative real-time PCR expression analysis

-

723788

cloned and expressed in Escherichia coli

-

640587

DNA sequence determination and analysis, promotor region footprinting, expression analysis, mechanism of the enzyme expression regulation

-

662283

fragments of the enzyme cloned into firefly luciferase plasmid

-

640596

fusion protein with maltose-binding protein

enzyme expression is reduced by 5% by bezafibrate

-

723788

insulin is known to increase the enzyme expression in cultured rat hepatocytes

-

721483

overexpression of peroxisome proliferator-activated receptor gamma coactivator-1alpha does not increase the expression of the enzyme

739507

reconstitution with lipoylated recombinant E2